This invention relates to the purification of p-aminophenol and, more particularly, to a process for the recovery and extractive purification of p-aminophenol which more selectively removes the principal impurity of concern, namely, 4,4'-diaminodiphenyl ether.
p-Aminophenol (PAP) is a well known and important chemical intermediate used in the preparation of the analgesic, acetaminophen (APAP). It is also used as an intermediate in the production of dyestuffs and photographic chemicals. A high degree of purity, particularly with respect to 4,4'-diaminodiphenyl ether, is desirable for p-aminophenol especially as regards its use in the preparation of acetaminophen.
An important commercial and widely used method for the preparation of PAP involves the catalytic hydrogenation of nitrobenzene in a strongly acid medium. In the basic process, hydrogenation of nitrobenzene is carried out in the presence of a 10-13% sulfuric acid solution containing a small amount of a surfactant such as dodecyltrimethylammonium chloride, and employing a platinum-on-carbon catalyst. The reaction is somewhat complex and yields, in addition to the desired PAP, a significant amount of aniline as well as a number of minor amine by-products, including 4,4'-diaminodiphenyl ether (also known as oxydianiline or ODA), o-aminophenol, p-aminodiphenylamine and p-hydroxydiphenylamine. These by-products, which are potential impurities in the PAP end product, are generally soluble in the acidic aqueous media. 4,4'-Diaminodiphenyl ether is the principal minor amine byproduct and, for use of PAP in preparing pharmaceutical compounds, its presence therein should be less than 20 ppm and preferably less than 10 ppm.
In a particularly advantageous process for the preparation of PAP by the catalytic hydrogenation of nitrobenzene in aqueous sulfuric acid (see Benner U.S. Pat. application Ser. No. 3,383,416, dated May 14, 1968), the hydrogenation reaction is interrupted prior to the consumption of all the nitrobenzene charged into the reactor. The catalyst tends to suspend in the nitrobenzene layer, and the aqueous reaction mixture, containing the PAP, aniline and the minor amine byproducts in the form of salts, is readily separated by decantation.
As stated, PAP which is used in the preparation of APAP should preferably be quite pure, expecially with respect to 4,4'-diaminodiphenyl ether. A number of processes directed to improving the purification of p-aminophenol have been described in the patent literature. In addition to Benner U.S. Pat. Ser. No. 3,383,416, the following patents are pertinent to processes for preparing p-aminophenol:
U.S. Pat. No. 3,658,905
U.S. Pat. No. 3,694,508
U.S. Pat. No. 3,703,598
U.S. Pat. No. 3,717,680
U.S. Pat. No. 3,845,129
U.S. Pat. No. 3,876,703
U.S. Pat. No. 3,917,695
U.S. Pat. No. 4,139,562
U.S. Pat. No. 4,176,138
Brit. Pat. No. 1,028,078
Brit. Pat. No. 1,038,005
Brit. Pat. No. 1,228,568
Brit. Pat. No. 1,291,642
Brit. Pat. No. 1,516,380
Japanese Pat. No. SHO 54(1979)-73741
In Baron et al. U.S. Pat. Ser. No. 3,717,680, aniline is added to the aqueous reaction product from the basic Benner process and the pH is increased to a value above 6.0, preferably 6.5-7.5, at which the PAP is in the free amine form. The solution is then cooled and the PAP crystallizes out, is filtered off and washed, first with aniline and then with toluene. The aniline phase, containing 4,4'-diaminodiphenyl ether and other minor amine byproducts is then separated from the aqueous phase.
Japanese Pat. No. SHO 54(1979)-73741 discloses a process for producing purified p-aminophenol in which the catalytic reduction reaction mixture resulting from the catalytic reduction of nitrobenzene is partially neutralized with an alkali to a pH of 3.5 to 5. An aromatic amine such as aniline is then added and 4,4'-diaminodiphenyl ether and other impurities associated with sulfuric acid in the aqueous phase are selectively replaced with the aromatic amine. The liberated impurities are removed by extraction with excess aromatic amine. The aromatic amine phase recovered is washed with an aqueous alkali solution and recycled and used for the partial neutralization of the catalytic reduction reaction mixture.
Reid U.S. Pat. Ser. No. 3,845,129 discloses a process for the recovery of p-aminophenol in purified form prepared by catalytic reduction of nitrobenzene whereby aniline and 4,4'-diaminodiphenyl ether are present as impurities, the process involving contacting a solution of p-aminophenol and the impurities in an aqueous medium having a pH of 4.8 to 5.5, particularly 5.0 to 5.5, just short of that at which precipitation of p-aminophenol occurs and at which aniline and 4,4'-diaminodiphenyl ether are in the form of free bases with an extraction medium consisting essentially of a non-oxygenated solvent immiscible with water such as methylene dichloride, chloroform, carbon tetrachloride, etc. The solvent selectively dissolves the impurities and p-aminophenol of improved purity is recovered from the aqueous phase. Toluene is listed as being a relatively poor solvent for 4,4'-diaminodiphenyl ether.
Yamamoto U.S. Pat. Ser. No. 4,139,562 discloses a process for purifying crude p-aminophenol in which the latter obtained by catalytically reducing nitrobenzene in an aqeuous sulfuric acid medium is added with an alkali in an atmosphere of an inert gas, such as nitrogen, and in the presence of a reducing agent, such as sodium dithionite or sodium sulfite, to adjust the pH to 7-8 and the resulting precipitate of crude p-aminophenol is separated from the liquid phase. The separated p-aminophenol is then redissolved in an aqueous metal solution to form an aqueous solution of an alkali metal salt of crude p-aminophenol which is contacted with an inert organic solvent immiscible with water to permit the impurities present in the system to be selectively extracted in the organic solvent. The preferred organic solvent is aniline.
Sathe U.S. Pat. Ser. No. 4,176,138 discloses a method for preparing p-aminophenol by the catalytic hydrogenation of nitrobenzene in an acid reaction medium in which dimethyldodecylamine sulfate is substituted for trimethyldodecylammonium chloride to eliminate certain impurities.
Harmetz et al. U.S. Pat. Ser. No. 3,876,703 disclose a method of purifying crude p-aminophenol involving the preparation of a mixture of an aqueous solution of the crude p-aminophenol and nitrobenzene, adjusting the pH of the mixture to between 4.5 and 7.5 and separating a nitrobenzene phase.
While these purification schemes and others disclosed in the above-mentioned patent literature possess some degree of utility, a need continues to exist for a purification process which is more selective as to the removal of 4,4'-diaminodiphenyl ether from PAP, which provides PAP of improved purity in greater overall yields, and which avoids the losses of PAP inherent in the prior art processes.